Evaluation of parasitemia by qPCR in patients with chronic Chagas disease treated with benznidazole

Tycha Bianca Sabaini Pavan , Eros Antônio de Almeida , Rodrigo Gonçalves de Lima , Jamiro da Silva Wanderley , Luiz Cláudio Martins , Sandra Cecília Botelho Costa , Gláucia Elisete Barbosa Marcon

Asian Pacific Journal of Tropical Medicine ›› 2023, Vol. 16 ›› Issue (12) : 565 -572.

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Asian Pacific Journal of Tropical Medicine ›› 2023, Vol. 16 ›› Issue (12) :565 -572. DOI: 10.4103/1995-7645.391781
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Evaluation of parasitemia by qPCR in patients with chronic Chagas disease treated with benznidazole
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Abstract

Objective: To evaluate parasitemia by qPCR in patients undergoing etiological treatment and followed in a Brazilian reference center.

Methods: Parasite load was quantified by qPCR in 32 participants with chronic Chagas disease who were treated with benznidazole. Serological analyses were performed before and after the treatment and parasite loads were compared prior and 12/18 months post the treatment.

Results: Thirty-two participants were recruited and treated with benznidazole, and 20 were followed-up. Adverse events (AE) were observed in 22 out of 29 participants that had safety data (76%), and dermatological alterations were the most frequently observed AE. Of the 20 participants analyzed, 13 and 7 completed 12 and 18 months follow-up after the treatment, respectively. 12 Months after the final treatment, Trypanosoma cruzi was detectable in 3 patients by qPCR; 18 months after the final treatment, Trypanosoma cruzi was detectable per qPCR in 4 of the 7 participants. Thus, between 12 and 18 months, 7 participants of the 20 initial follow-up cases showed positive qPCR, indicating treatment failures.

Conclusions: qPCR can be used as an alternative method for evaluating the effectiveness of the etiological treatment of CD, and can be applied to analyze early therapeutic failures. The study showed that benznidazole therapy had limited effectiveness in treating chronic CD patients, thus emphasizing the importance of conducting continued research for developing more effective therapies and diagnosis for CD.

Keywords

Chagas disease / Antitrypanosomal therapy / Benznidazole / qPCR / Therapeutic failure

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Tycha Bianca Sabaini Pavan, Eros Antônio de Almeida, Rodrigo Gonçalves de Lima, Jamiro da Silva Wanderley, Luiz Cláudio Martins, Sandra Cecília Botelho Costa, Gláucia Elisete Barbosa Marcon. Evaluation of parasitemia by qPCR in patients with chronic Chagas disease treated with benznidazole. Asian Pacific Journal of Tropical Medicine, 2023, 16 (12) : 565-572 DOI:10.4103/1995-7645.391781

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References

[1]

Dias JCP, Ramos AN, Gontijo ED, Luquetti A, Shikanai-Yasuda MA, Coura JR, et al. II Consenso Brasileiro em Doença de Chagas, 2015. [Brazilian Consensus on Chagas Disease, 2015] Epidemiol Serv Saúde 2016; 25(esp): 7-86. doi: 10.5123/S1679-49742016000500002.

[2]

World Health Organization. Chagas disease in Latin America: An epidemiological update based on 2010 estimates. Wkly Epidemiol Rec 2015; 90(6): 33-43.

[3]

Shikanai-Yasuda MA, Albajar Viñas P. Endemic diseases: Globalization, urbanization, and immunosuppression. J Trop Med 2013; 2013: Article ID 390986. doi: 10.1155/2013/390986.

[4]

Viotti R, Alarcón De Noya B, Araujo-Jorge T, Grijalva MJ, Guhl F, López MC, et al. Towards a paradigm shift in the treatment of chronic Chagas disease. Antimicrob Agents Chemother 2014; 58(2): 635-639. doi: 10.1128/AAC.01662-13.

[5]

Morillo CA, Marin-Neto JA, Avezum A, Sosa-Estani S, Rassi A, Rosas F, et al. Randomized trial of benznidazole for chronic Chagas’ cardiomyopathy. N Engl J Med 2015; 373(14): 1295-1306. doi: 10.1056/NEJMoa1507574.

[6]

Bern C, Montgomery SP, Herwaldt BL, Rassi A, Marin-Neto JA, Dantas RO, et al. Evaluation and treatment of Chagas disease in the United States: A systematic review. J Am Med Assoc 2007; 298(18): 2171-2181. doi: 10.1001/jama.298.18.2171.

[7]

Gallerano RH, Sosa RR. Resultados de un estudio a largo plazo con drogas antiparasitarias en infectados chagásicos crónicos. Rev Fed Arg Cardiol 2001; 30(2): 289-296.

[8]

Garcia S, Ramos CO, Senra JFV, Vilas-Boas F, Rodrigues MM, Campos-De-Carvalho AC, et al. Treatment with benznidazole during the chronic phase of experimental Chagas’ disease decreases cardiac alterations. Antimicrob Agents Chemother 2005; 49(4): 1521-1528. doi: 10.1128/AAC.49.4.1521-1528.2005.

[9]

Sturm NR, Degrave W, Morel C, Simpson L. Sensitive detection and schizodeme classification of Trypanosoma cruzi cells by amplification of kinetoplast minicircle DNA sequences: Use in diagnosis of Chagas’ disease. Mol Biochem Parasitol 1989; 33(3): 205-214. doi: 10.1016/0166-6851(89)90082-0.

[10]

Piron M, Fisa R, Casamitjana N, López-Chejade P, Puig L, Vergés M, et al. Development of a real-time PCR assay for Trypanosoma cruzi detection in blood samples. Acta Trop 2007; 103(3): 195-200. doi: 10.1016/j.actatropica.2007.05.019.

[11]

Ciapponi A, Barreira F, Perelli L, Bardach A, Gascón J, Molina I, et al. Direct evidence gap on fixed versus adjusted-dose benznidazole for adults with chronic Chagas disease without cardiomyopathy: Systematic review and individual patient data meta-analysis. Trop Med Int Heal 2023; 28(1): 2-16. doi: 10.1111/tmi.13831.

[12]

Carvalho NB, de Freitas VT, Bezerra RC, Nakanishi ES, Velloso EP, Higashino HR, et al. Aplastic anemia and Chagas disease: Tcruzi parasitemia monitoring by quantitative PCR and preemptive antiparasitic therapy. Trop Med Infect Dis 2022; 7(10): 268. doi: 10.3390/tropicalmed7100268.

[13]

National Health Surveillance Agency (Anvisa). Notivisa–sistema nacional de notificações para a vigilância Sanitária. Anexo 3: Formulário para notificação de eventos adversos à medicamento–profissional da saúde. [Online]. Available from: https://antigo.anvisa.gov.br/documents/33868/379890/ea_medicamento_profissional.pdf/cdc25729-481d-4ad2-b57d-f1c8db23fda4?version=1.0. [Accessed on 17 December 2023].

[14]

Moreira OC, Ramírez JD, Velázquez E, Melo MFAD, Lima-Ferreira C, Guhl F, et al. Towards the establishment of a consensus real-time qPCR to monitor Trypanosoma cruzi parasitemia in patients with chronic Chagas disease cardiomyopathy: A substudy from the BENEFIT trial. Acta Trop 2013; 125(1): 23-31. doi: 10.1016/j.actatropica.2012.08.020.

[15]

Molina I, Gomez I Prat J, Salvador F, Treviño B, Sulleiro E, Serre N, et al. Randomized trial of posaconazole and benznidazole for chronic Chagas’ disease. N Engl J Med 2014; 370(20): 1899-1908. doi: 10.1056/NEJMoa1313122.

[16]

Niborski LL, Grippo V, Lafón SO, Levitus G, García-Bournissen F, Ramirez JC, et al. Serological based monitoring of a cohort of patients with chronic Chagas disease treated with benznidazole in a highly endemic area of northern Argentina. Mem Inst Oswaldo Cruz 2016; 111(6): 365-371. doi: 10.1590/0074-02760160006.

[17]

Caldas IS, Santos EG, Novaes RD. An evaluation of benznidazole as a Chagas disease therapeutic. Expert Opin Pharmacother 2019; 20(15): 1797-1807. doi: 10.1080/14656566.2019.1650915.

[18]

Alonso-Vega C, Urbina JA, Sanz S, Pinazo MJ, Pinto JJ, Gonzalez VR, et al. New chemotherapy regimens and biomarkers for Chagas disease: The rationale and design of the TESEO study, an open-label, randomised, prospective, phase-2 clinical trial in the Plurinational State of Bolivia. BMJ Open 2021; 11(12): e052897. doi: 10.1136/bmjopen-2021-052897.

[19]

Sguassero Y, Cuesta CB, Roberts KN, Hicks E, Comandé D, Ciapponi A, et al. Course of chronic Trypanosoma cruzi infection after treatment based on parasitological and serological tests: A systematic review of follow-up studies. PLoS One 2015; 10(10): 1-23. doi: 10.1371/journal.pone.0139363.

[20]

Schijman AG. Molecular diagnosis of Trypanosoma cruzi. Acta Trop 2018; 184: 59-66. doi: 10.1016/j.actatropica.2018.02.019.

[21]

Britto CC. Usefulness of PCR-based assays to assess drug efficacy in Chagas disease chemotherapy: Value and limitations. Mem Inst Oswaldo Cruz 2009; 104(Suppl 1): 122-135. doi: 10.1590/S0074-02762009000900018.

[22]

Zingales B. Trypanosoma cruzi genetic diversity: Something new for something known about Chagas disease manifestations, serodiagnosis and drug sensitivity. Acta Trop 2018; 184: 38-52. doi: 10.1016/j.actatropica.2017.09.017.

[23]

Guimarães-Pinto K, Ferreira JRM, da Costa ALA, Morrot A, Freire-de-Lima L, Decote-Ricardo D, et al. Cellular stress and senescence induction during Trypanosoma cruzi infection. Trop Med Infect Dis 2022; 7(7): 129. doi: 10.3390/tropicalmed7070129.

[24]

Murcia L, Carrilero B, Munoz MJ, Iborra MA, Segovia M. Usefulness of PCR for monitoring benznidazole response in patients with chronic Chagas’ disease: A prospective study in a non-disease-endemic country. J Antimicrob Chemother 2010; 65(8): 1759-1764. doi: 10.1093/jac/dkq201.

[25]

Ramírez JC, Parrado R, Sulleiro E, De La Barra A, Rodríguez M, Villarroel S, et al. First external quality assurance program for bloodstream Real-Time PCR monitoring of treatment response in clinical trials of Chagas disease. PLoS One 2017; 12(11): 1-15. doi: 10.1371/journal.pone.0188550.

[26]

Pérez-Molina JA, Pérez-Ayala A, Moreno S, Fernández-González MC, Zamora J, López-Velez R. Use of benznidazole to treat chronic Chagas’ disease: A systematic review with a meta-analysis. J Antimicrob Chemother 2009; 64(6): 1139-1147. doi: 10.1093/jac/dkp357.

[27]

Yun O, Lima MA, Ellman T, Chambi W, Castillo S, Flevaud L, et al. Feasibility, drug safety, and effectiveness of etiological treatment programs for Chagas disease in honduras, guatemala, and bolivia: 10-Year experience of médecins sans frontières. PLoS Negl Trop Dis 2009; 3(7): e488. doi: 10.1371/journal.pntd.0000488.

[28]

Momper JD, Hanan NJ, Rossi SS, Mirochnick MH, Cafferata ML, Lavenia A, et al. Determination of benznidazole in human dried blood spots by liquid chromatography–mass spectrometry to monitor adherence to Trypanosoma cruzi infection treatment in infants and children. Am J Trop Med Hyg 2019; 101(1): 116-122. doi: 10.4269/ajtmh.18-0852.

[29]

Murcia L, Carrilero B, Ferrer F, Roig M, Franco F, Segovia M. Success of benznidazole chemotherapy in chronic Trypanosoma cruzi-infected patients with a sustained negative PCR result. Eur J Clin Microbiol Infect Dis 2016; 35(11): 1819-1827. doi: 10.1007/s10096-016-2733-6.

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